CN106588745B - A kind of intermediate and its preparation method and application of benzo alkene fluorine bacterium azoles - Google Patents
A kind of intermediate and its preparation method and application of benzo alkene fluorine bacterium azoles Download PDFInfo
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/44—Iso-indoles; Hydrogenated iso-indoles
- C07D209/48—Iso-indoles; Hydrogenated iso-indoles with oxygen atoms in positions 1 and 3, e.g. phthalimide
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- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C201/00—Preparation of esters of nitric or nitrous acid or of compounds containing nitro or nitroso groups bound to a carbon skeleton
- C07C201/06—Preparation of nitro compounds
- C07C201/12—Preparation of nitro compounds by reactions not involving the formation of nitro groups
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- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C213/00—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton
- C07C213/02—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton by reactions involving the formation of amino groups from compounds containing hydroxy groups or etherified or esterified hydroxy groups
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/14—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
Abstract
The present invention provides a kind of intermediate and its preparation method and application of benzo alkene fluorine bacterium azoles, and the compound is N- (1,2,3,4- tetrahydro-Isosorbide-5-Nitrae-endo-methylene group-naphthalene -9- phenol -5- base -)-phthalimide, shown in chemical formula such as formula (VI):
Description
Technical field
The present invention relates to the intermediate of benzo alkene fluorine bacterium azoles, i.e., new compound N-(1,2,3,4- tetrahydro-Isosorbide-5-Nitrae-bridge methylene
Base-naphthalene -9- phenol -5- base -)-phthalimide, and its preparation method and application.
Background technique
Benzo alkene fluorine bacterium azoles (benzovindiflupyr also known as SYN545192, trade name Solatenol) are a kind of tools
There is the succinate dehydrogenase fungicide of novel binding mode.Benzo alkene fluorine bacterium azoles wide spectrum, efficiently, makees with more efficient sterilization
With can prevent and treat foliage disease and soil surface characters extensively, be important resistance management tool, in wheat, corn and extraordinary make
The outstanding control efficiency to Major Diseases is all presented on many crops such as object.The product to wheat leaf blight, the cercospora black spot of peanut,
Take-all and wheat basal stem rot have good control efficiency, especially to wheat powdery mildew, corn southern leaf blight and gray mold
There is special efficacy, there is outstanding control efficiency to Asian Soybean Rust, without cross-resistance with existing fungicides is a great potential
Fungicide.
Benzo alkene fluorine bacterium azoles are the pyrazol acid amide fungicide for being taken the lead in developing by Syngenta Co., Ltd, and 2013, Du Pont was public
Department also assists in the market exploitation of benzo alkene fluorine bacterium azoles.Now by Syngenta and Du Pont's joint development.So far there is numerous patents Jie
The chemical synthesis process for the benzo alkene fluorine bacterium azoles that continued, mainly there is WO2011131545, WO2011131544, WO2011131546,
WO2010049228 etc..
But route reported at present is respectively present that yield is low, and raw material is difficult to obtain, intermediate stability is poor, operation
The disadvantages of complexity, severe reaction conditions, unsuitable large-scale industrial production.
The synthetic route reported in WO2011131546 is visible shortest synthetic route in document so far, but
It is starting material 6,6- dichloro fulvene is unstable, it needs oneself to synthesize, thus step is still long, total recovery is relatively low；Secondly should
Method is laboratory process, therefore is also unsuitable for large-scale industrial production.
Inventor has carried out 3- difluoromethyl -1- methyl-1 H- pyrazoles -4- carboxylic acid-(9- dichloromethylene -1,2,3,4- four
Hydrogen-Isosorbide-5-Nitrae-endo-methylene group-naphthalene -5- base)-amide, that is, benzo alkene fluorine bacterium azoles chemical synthesis process exploration, provide a kind of receipts
Rate is high, and reaction condition is mild, and easy to operation, good product quality, the method for being suitable for large-scale industrial production, this makes a living
It produces benzo alkene fluorine bacterium azoles and provides the higher selection of another feasibility, and synthesized in a kind of new compound in the process
The bromo- 5- nitro -1,2 of mesosome 2-, 3,4- tetrahydros-Isosorbide-5-Nitrae-endo-methylene group-naphthalene -9- phenol, the intermediate can be used to synthesize benzo alkene fluorine
Bacterium azoles.
Summary of the invention
The present invention provides a kind of compounds, can be used as the intermediate of synthesis benzo alkene fluorine bacterium azoles with the compound, described
Compound be N- (1,2,3,4- tetrahydro-Isosorbide-5-Nitrae-endo-methylene group-naphthalene -9- phenol -5- base -)-phthalimide, chemical formula
As shown in formula (VI):
The above compound N-(1,2,3,4- tetrahydro -1,4- endo-methylene group-naphthalene -9- phenol-is prepared the present invention also provides a kind of
5- base -)-phthalimide method, the method is with such as formula (V) compound represented 5- amino -1,23,4-
Tetrahydro-Isosorbide-5-Nitrae-endo-methylene group-naphthalene -9- phenol and phthalic anhydride after reaction, are added organic molten under high temperature fused state
Agent, is made formula (VI) compound, and the organic solvent is toluene, dimethylbenzene, chlorobenzene, cyclopentanone etc..
Further, the mass ratio of the material that feeds intake in the method is compound (V): phthalic anhydride 1: 1.01-
1.2, preferably 1:1.05.The consumption of organic solvent (quality) is 2 times of compound (V) quality.
Further, the high temperature is 120 DEG C -150 DEG C, preferably 130 DEG C.
Further, the preferred dimethylbenzene of the organic solvent.
Further, the compound N-(1,2,3,4- tetrahydro-Isosorbide-5-Nitrae-endo-methylene group-naphthalene -9- phenol -5- base -)-is prepared
The method of phthalimide are as follows: the 5- amino -1,2,3,4- tetrahydro -1,4- endo-methylene group-naphthalene -9- phenol and adjacent benzene two
At 130 DEG C after reaction, dimethylbenzene is added dropwise in formic anhydride while hot, and formula (VI) compound is made.
In the adjacent benzene two of the preparation compound N-(1,2,3,4- tetrahydro -1,4- endo-methylene group-naphthalene -9- phenol -5- base -) -
In the method for carboximide, formula (V) compound can be made by following methods: the bromo- 5- nitro -1,2 of 2-, 3,4- tetrahydro -1,
4- endo-methylene group-naphthalene -9- phenol (IV) and with Pd/C and organic base, under Hydrogen Vapor Pressure in alcoholic solvent, at 120 DEG C react life
At 5- amino -1,2,3,4- tetrahydro -1,4- endo-methylene group-naphthalene -9- phenol (V).
The mass ratio that feeds intake of formula (IV) compound and Pd/C is 1: 0.01-0.05, preferably 1:0.03.
The Hydrogen Vapor Pressure is 2.0MPa-3.5MPa, preferably 3.0MPa.
The alcoholic solvent is anhydrous methanol or dehydrated alcohol, and the organic base is triethylamine.
Processing step is as follows:
1) 5- nitro -1,4- dihydro -1,4- endo-methylene group-naphthalene preparation
By methylene chloride, catalyst I is added in reaction kettle, and co-catalyst II and 2- ammonia is added dropwise simultaneously under 40 DEG C of stirrings
The acetone soln of base -6- nitrobenzoic acid, cyclopentadiene after charging, is warming up to 50 DEG C and is stirred to react 3h, wait react knot
Beam, reaction solution are filtered with diatomite, filtrate concentration, and use n-hexane refluxing extraction, obtain 5- nitro-Isosorbide-5-Nitrae-dihydro-Isosorbide-5-Nitrae-bridge Asia
Methyl-naphthalene, the catalyst I are the concentrated sulfuric acid, and the co-catalyst II is isoamyl nitrite or nitrite tert-butyl；
2) [2,3]-epoxy -5- nitro -1,2,3,4- tetrahydro -1,4- endo-methylene group-naphthalene preparation
5- nitro -1,4- dihydro -1,4- endo-methylene group-the naphthalene and 1,2- dichloroethanes wiring solution-forming that step 1) is obtained；
Metachloroperbenzoic acid is added into reaction kettle, with 1,2- dichloroethanes for solvent, stirs lower dropwise addition 5- nitro-Isosorbide-5-Nitrae-dihydro-
Isosorbide-5-Nitrae-endo-methylene group-naphthalene solution, charging terminate, and are warming up to 60 DEG C and are stirred to react 1.5h, after reaction, saturation sulfurous acid are added
Sodium solution, liquid separation, organic layer alkali cleaning, concentration obtain [2,3]-epoxy -5- nitro -1,2,3,4- tetrahydros-Isosorbide-5-Nitrae-endo-methylene group-naphthalene；
3) the bromo- 5- nitro -1,2,3,4- tetrahydro -1,4- endo-methylene group of 2--naphthalene -9- phenol preparation
[2,3]-epoxy -5- nitro -1,2,3,4- tetrahydro -1,4- endo-methylene group-naphthalene that step 2) is obtained and organic molten
Agent wiring solution-forming；Hydrobromic acid aqueous solution is added into reaction kettle, at 20 DEG C, dropwise addition [2,3]-epoxy -5- nitro -1,2,3,4-
Tetrahydro-Isosorbide-5-Nitrae-endo-methylene group-naphthalene solution, charging terminate, and are stirred to react 5min, after reaction, liquid separation, during organic layer is washed till
Property after, dry, concentration obtains the bromo- 5- nitro -1,2 of 2-, 3,4- tetrahydros-Isosorbide-5-Nitrae-endo-methylene group-naphthalene -9- phenol；
4) 5- amino -1,2,3,4- tetrahydro -1,4- endo-methylene group-naphthalene -9- phenol preparation
Reaction kettle is added in the bromo- 5- nitro -1,2,3,4- tetrahydro -1,4- endo-methylene group of the 2- that step 3) is obtained-naphthalene -9- phenol
In, using dehydrated alcohol or anhydrous methanol as solvent, metallic catalyst IV and co-catalyst V is added, heats up and stirs under Hydrogen Vapor Pressure
Reaction 5-6 hours is mixed, to fully reacting, reaction solution is filtered, filtrate is distilled to recover solvent, obtains 5- amino -1,2,3,4- tetrahydros -
Isosorbide-5-Nitrae-endo-methylene group-naphthalene -9- phenol, the metallic catalyst IV are any one in Pd/C, Rh/C, Pt/C or Raney's nickel, institute
Stating co-catalyst V is any one in triethylamine, diisopropylethylamine or pyridine；
5) preparation of N- (1,2,3,4- tetrahydro -1,4- endo-methylene group-naphthalene -9- phenol -5- base -)-phthalimide
5- amino -1,2 that step 4) is obtained, 3,4- tetrahydros-Isosorbide-5-Nitrae-endo-methylene group-naphthalene -9- phenol are added in reaction kettle, add
Enter phthalic anhydride, heating melting under solvent-free conditions is stirred to react 1.5h, and to the end of reacting, organic solvent is added dropwise while hot
VI, after being cooled to room temperature, filtering obtains shallow white solid N- (1,2,3,4- tetrahydro-Isosorbide-5-Nitrae-endo-methylene group-naphthalene -9- phenol -5- base -) -
Phthalimide, the organic solvent VI are any one in dimethylbenzene, cyclopentanone, chlorobenzene or toluene.
Wherein,
Step 1) the catalyst I is the concentrated sulfuric acid, and the molar ratio of 2- amino -6- nitrobenzoic acid and the concentrated sulfuric acid is 1:
0.01。
The concentration of the step 3) hydrobromic acid aqueous solution be 48% hydrobromic acid aqueous solution, [2,3]-epoxy -5- nitro -1,2,
The molar ratio of 3,4- tetrahydro -1,4- endo-methylene group-naphthalene and 48% hydrobromic acid aqueous solution is 1:1-20.
Organic solvent II I described in step 3) is appointing in methylene chloride, ethyl acetate, tetrahydrofuran, acetonitrile or chlorobenzene
It anticipates one kind.
Step 4) the metallic catalyst IV is 5%Pd/C；The bromo- 5- nitro -1,2,3,4- tetrahydro -1,4- bridge methylene of 2-
The mass ratio of base-naphthalene -9- phenol and metallic catalyst IV are 1:0.01-0.05.
Co-catalyst V described in step 4) is triethylamine；The bromo- 5- nitro -1,2,3,4- tetrahydro -1,4- endo-methylene group-of 2-
The molar ratio of naphthalene -9- phenol and co-catalyst V are 1:2-5.
Step 4) the Hydrogen Vapor Pressure is 2.0-3.5MPa, and reaction temperature is 120 DEG C.
Step 5) 5- amino -1,2,3,4- tetrahydro -1,4- endo-methylene group-naphthalene -9- the phenol and phthalic anhydride rub
, than being 1:1.01-1.2, reaction temperature is 120-150 DEG C for you.
Step 5) the organic solvent VI is dimethylbenzene, 5- amino -1,2,3,4- tetrahydros-Isosorbide-5-Nitrae-endo-methylene group-naphthalene -9- phenol
Mass ratio with dimethylbenzene is 1:2.
In addition the present invention provides compound N-(1,2,3,4- tetrahydro -1,4- endo-methylene group-naphthalene -9- phenol -5- base -)-neighbours
Phthalimide (VI) prepares N- (1,2,3,4- tetrahydro -1,4- endo-methylene group-naphthalene -9- carbonyl -5- base -)-phthalyl
Imines (VII), the application of final obtained benzo alkene fluorine bacterium azoles, specific described formula (VII) compound is shown in formula (VI)
N- (1,2,3,4- tetrahydro-Isosorbide-5-Nitrae-endo-methylene group-naphthalene -9- phenol -5- base -)-phthalimide be raw material, in ethyl acetate
In with trichloroisocyanuric acid (TCCA), sodium bromide, under 2, the catalysis of 2,6,6- tetramethyl piperidines-nitrogen-oxide (TEMPO) in
0 DEG C of reaction generates formula (VII) compound represented.
The formula (VI): TEMPO:TCCA: the ratio of the amount of the substance of sodium bromide is 1:0.01-0.1:1.0-1.5:0.1-
0.5, preferred proportion is compound (VI): TEMPO:TCCA: the ratio of the amount of the substance of sodium bromide is 1:0.02:1.3:0.2.
The adjacent benzene two of compound N-(1,2,3,4- tetrahydro -1,4- endo-methylene group-naphthalene -9- carbonyl -5- base -)-as described above
Carboximide (VII) can be used to prepare N- (1,2,3,4- tetrahydro -1,4- endo-methylene group-naphthalene -9- dichloro methene -5- base -)-neighbour
Phthalimide (VIII), finally benzo alkene fluorine bacterium azoles are made, specific described formula (VIII) compound is with formula
(VII) (1,2,3,4- tetrahydro -1,4- endo-methylene group-naphthalene -9- carbonyl -5- base -)-phthalimide of N- shown in is original
Material is reacted at 60 DEG C -65 DEG C under the protection of nitrogen with triphenylphosphine and carbon tetrachloride in acetonitrile and is generated shown in formula (VII)
Compound.
The ratio of the amount of the substance of the formula (VII) and triphenylphosphine and carbon tetrachloride is 1:3:2.
Compound N-(1,2,3,4- tetrahydro -1,4- endo-methylene group-naphthalene -9- dichloro methene -5- base -)-as described above
Phthalimide (VIII) can be used to prepare -1,2,3,4- tetrahydro -5- amino naphthalenes (IX) of 9- (dichloro methene), final to use
Benzo alkene fluorine bacterium azoles are made, specific described formula (IX) compound is with N- (1,2,3,4- tetrahydro-shown in formula (VIII)
Isosorbide-5-Nitrae-endo-methylene group-naphthalene -9- dichloro methene -5- base -)-phthalimide be raw material, in alcoholic solvent with alkaline reagent
Reaction generates formula (IX) compound represented at 90 DEG C.The alcoholic solvent is methanol or ethyl alcohol, and the alkaline reagent is
40% methylamine water solution or 80% hydrazine hydrate solution.
The ratio of the amount of the substance of the formula (VIII) and alkaline reagent is 1:1-8, preferably 1:4.
Compound 9- (dichloro methene) -1,2,3,4- tetrahydro -5- amino naphthalenes (IX) as described above can be used to that benzene is made
And alkene fluorine bacterium azoles, specific described formula (X) compound is with 9- shown in formula (IX) (dichloro methene) -1,2,3,4- tetra-
Hydrogen -5- amino naphthalenes are raw material, with 3- difluoromethyl -1- methyl-1 H- pyrazoles -4- phosgene 0 in organic solvent and triethylamine
Reaction generates formula (X) compound represented at DEG C.The organic solvent is ethyl acetate, butyl acetate, methylene chloride, 1,2-
Any one in dichloroethanes, toluene, dimethylbenzene or chlorobenzene, preferably methylene chloride.
The ratio of the amount of the substance of the formula (IX) and 3- difluoromethyl -1- methyl-1 H- pyrazoles -4- phosgene is 1:
1.01。
The present invention can be such that the preparation of benzo alkene fluorine bacterium azoles prepares by following route, and reaction equation is expressed as follows:
By using above-mentioned technology, compared with prior art, contribution of the invention is:
1) compound (III) directly reacts to obtain compound (IV) with hydrobromic acid aqueous solution, and the compound is chemically
Matter is stablized, and the presence of unstable intermediate is avoided；It has found a kind of new to produce benzo alkene fluorine bacterium azoles key intermediate
And its preparation method, make synthesize benzo alkene fluorine bacterium azoles route it is more reasonable, and find in the process new compound N-(1,
2,3,4- tetrahydro -1,4- endo-methylene group-naphthalene -9- phenol -5- base -)-phthalimide (VI).
2) compound (IV) avoids the zinc generated using will lead to a large amount of solid wastes using Pd/C catalysis reduction-debromination reaction
Powder, it is at low cost, it is environmental-friendly.
3) in the preparation process of benzo alkene fluorine bacterium azoles, compound (V) is first protected with phthalic anhydride cheap and easy to get, last
Step connects expensive 1H- pyrazoles segment, avoids the waste of expensive reagent, and the upper protection and deprotection process production of phthalic anhydride
Rate is high, and easy to operation, reaction condition is mild, good product quality, is the method for being suitable for large-scale industrial production.
Specific embodiment
Below the technical scheme of the invention is illustrated by a specific example, but the scope of the present invention is not limited thereto:
1 N- of embodiment (1,2,3,4- tetrahydro -1,4- endo-methylene group-naphthalene -9- phenol -5- base -)-phthalimide
(VI) synthesis.
The mass ratio of the material that feeds intake is 5- amino -1,2,3,4- tetrahydro -1,4- endo-methylene group-naphthalene -9- phenol: phthalic anhydride
=1:1.05.
Mechanical stirring is being housed, in the 500ml four-hole bottle of thermometer, 5- amino -1,2 is being added, 3,4- tetrahydros-Isosorbide-5-Nitrae-bridge is sub-
Methyl-naphthalene -9- phenol (99.8g, 0.57mol), phthalic anhydride (88.5g, 0.59mol) are warming up to 130 DEG C, stir 1.5h,
After reaction, while hot be added dropwise toluene 200ml, finish, after cooled to room temperature, filtering, obtain N- (1,2,3,4- tetrahydro -1,
4- endo-methylene group-naphthalene -9- phenol -5- base -)-phthalimide (VI) 167.3g, yield 96.2%, fusing point 148.9-149.7
℃。
2 N- of embodiment (1,2,3,4- tetrahydro -1,4- endo-methylene group-naphthalene -9- phenol -5- base -)-phthalimide
(VI) synthesis.
The mass ratio of the material that feeds intake is 5- amino -1,2,3,4- tetrahydro -1,4- endo-methylene group-naphthalene -9- phenol: phthalic anhydride
=1:1.01.
Mechanical stirring is being housed, in the 500ml four-hole bottle of thermometer, 5- amino -1,2 is being added, 3,4- tetrahydros-Isosorbide-5-Nitrae-bridge is sub-
Methyl-naphthalene -9- phenol (99.8g, 0.57mol), phthalic anhydride (85.8g, 0.58mol) are warming up to 150 DEG C, stir 1.5h,
After reaction, while hot be added dropwise toluene 200ml, finish, after cooled to room temperature, filtering, obtain N- (1,2,3,4- tetrahydro -1,
4- endo-methylene group-naphthalene -9- phenol -5- base -)-phthalimide (VI) 158.2g, yield 90.1%, fusing point 148.8-149.9
℃。
3 N- of embodiment (1,2,3,4- tetrahydro -1,4- endo-methylene group-naphthalene -9- phenol -5- base -)-phthalimide
(VI) synthesis.
The mass ratio of the material that feeds intake is 5- amino -1,2,3,4- tetrahydro -1,4- endo-methylene group-naphthalene -9- phenol: phthalic anhydride
=1:1.2.
Mechanical stirring is being housed, in the 500ml four-hole bottle of thermometer, 5- amino -1,2 is being added, 3,4- tetrahydros-Isosorbide-5-Nitrae-bridge is sub-
Methyl-naphthalene -9- phenol (99.8g, 0.57mol), phthalic anhydride (100.6g, 0.68mol) are warming up to 120 DEG C, stirring
Toluene 200ml is added dropwise while hot, finishes after reaction by 1.5h, and after cooled to room temperature, filtering obtains N- (1,2,3,4- tetra-
Hydrogen-Isosorbide-5-Nitrae-endo-methylene group-naphthalene -9- phenol -5- base -)-phthalimide (VI) 162.6g, yield 93.5%, fusing point 148.9-
149.9℃。
The synthesis of 4 5- nitro -1,4- dihydro -1,4- endo-methylene group of embodiment-naphthalene (II)
The mass ratio of the material that feeds intake is 2- amino -6- nitrobenzoic acid (I): cyclopentadiene: isoamyl nitrite: the concentrated sulfuric acid=
1:3:1.2:0.01
In the 500ml there-necked flask equipped with mechanical stirring, constant pressure funnel and thermometer, 170ml methylene chloride is added
With the concentrated sulfuric acid (0.098g, 0.001mol), isoamyl nitrite (14.1g, 0.12mol), 2- amino-is added dropwise simultaneously at 40 DEG C
The acetone soln of 6- nitrobenzoic acid (18.2g, 0.1mol) and cyclopentadiene (19.8g, 0.3mol).Feed time control exists
1h is warming up to 50 DEG C of stirring 3h and is cooled to room temperature after reaction after charging, reaction solution is filtered with diatomite, and filtrate is dense
After contracting, with n-hexane refluxing extraction 3 times, merges n-hexane, 5- nitro-Isosorbide-5-Nitrae-dihydro-Isosorbide-5-Nitrae-endo-methylene group-naphthalene is obtained after concentration
(II) 14.9g, yield 74.6%, [the GC method: Fu Li 9790II type gas chromatograph of G/C content 97.3%；Chromatographic column: SE-54；Into
Sample device: 330 DEG C；Detector: 340 DEG C；Column temperature: 250 DEG C].
The synthesis of 5 5- nitro -1,4- dihydro -1,4- endo-methylene group of embodiment-naphthalene (II)
The mass ratio of the material that feeds intake is 2- amino -6- nitrobenzoic acid (I): cyclopentadiene: isoamyl nitrite: the concentrated sulfuric acid=
1:2:1.2:0.01
The inventory of cyclopentadiene is 13.2g, remaining inventory and operating condition with embodiment 8, obtains 5- nitro-Isosorbide-5-Nitrae-two
Hydrogen-Isosorbide-5-Nitrae-endo-methylene group-naphthalene (II) 11.4g, yield 60.9%, G/C content 98.4%.Vapor detection condition is the same as embodiment 4.
The synthesis of 6 5- nitro -1,4- dihydro -1,4- endo-methylene group of embodiment-naphthalene (II)
The mass ratio of the material that feeds intake is 2- amino -6- nitrobenzoic acid (I): cyclopentadiene: isoamyl nitrite: the concentrated sulfuric acid=
1:18:1.2:0.01
The inventory of cyclopentadiene is 118.8g, remaining inventory and operating condition with embodiment 8, obtains 5- nitro-Isosorbide-5-Nitrae-
Dihydro-Isosorbide-5-Nitrae-endo-methylene group-naphthalene (II) 14.7g, yield 70.6%, G/C content 96.8%.Vapor detection condition is the same as embodiment 4.
Embodiment 7 [2,3]-epoxy -5- nitro -1,2,3,4- tetrahydro -1,4- endo-methylene group-naphthalene (III) synthesis
The mass ratio of the material that feeds intake is 5- nitro -1,4- dihydro -1,4- endo-methylene group-naphthalene (II): metachloroperbenzoic acid=
1:1.5。
In the 1000ml there-necked flask equipped with mechanical stirring, constant pressure funnel and thermometer, 75% m-chloro peroxide is added
Benzoic acid (86.3g, 0.375mol) and 1,2- dichloroethanes (500ml) open stirring, at room temperature, nitro -1 5- are slowly added dropwise,
1,2- dichloroethanes (100ml) solution of 4- dihydro-Isosorbide-5-Nitrae-endo-methylene group-naphthalene (47.0g, 0.25mol) drips after 0.5h
Finish, then heats to 60 DEG C, stir 1.5h at 60 DEG C.After reaction, 100ml saturated sodium sulfite is added into reaction solution
Solution, after stirring 10min, filtering, filtrate stratification.Organic layer is washed till neutrality with saturated sodium bicarbonate solution 1000ml, then
It is primary with saturated common salt washing, it is evaporated under reduced pressure after recycling 1,2- dichloroethanes and obtains [2,3]-epoxy -5- nitro -1,2,3,4- tetra-
Hydrogen-Isosorbide-5-Nitrae-endo-methylene group-naphthalene (III) 49.8g, yield 98.1%, G/C content 97.4%.Vapor detection condition is the same as embodiment 4.
Embodiment 8 [2,3]-epoxy -5- nitro -1,2,3,4- tetrahydro -1,4- endo-methylene group-naphthalene (III) synthesis
The mass ratio of the material that feeds intake is 5- nitro -1,4- dihydro -1,4- endo-methylene group-naphthalene (II): metachloroperbenzoic acid=
1:1.1
The inventory of 75% metachloroperbenzoic acid metachloroperbenzoic acid is 63.3g, remaining inventory and operating condition
With embodiment 5, [2,3]-epoxy -5- nitro -1,2,3,4- tetrahydros-Isosorbide-5-Nitrae-endo-methylene group-naphthalene (III) 41.6g, yield are obtained
81.9%, G/C content 98.2%, vapor detection condition is the same as embodiment 4.
Embodiment 9 [2,3]-epoxy -5- nitro -1,2,3,4- tetrahydro -1,4- endo-methylene group-naphthalene (III) synthesis
The mass ratio of the material that feeds intake is 5- nitro -1,4- dihydro -1,4- endo-methylene group-naphthalene (II): metachloroperbenzoic acid=
1:1.6
The inventory of 75% metachloroperbenzoic acid metachloroperbenzoic acid is 92.0g, and reaction temperature is 80 DEG C, remaining throwing
Doses and operating condition obtain [2,3]-epoxy -5- nitro -1,2,3,4- tetrahydros-Isosorbide-5-Nitrae-endo-methylene group-naphthalene (III) with embodiment 5
46.7g, yield 92.0%, G/C content 96.4%, vapor detection condition is the same as embodiment 4.
The synthesis of the bromo- 5- nitro -1,2,3,4- tetrahydro -1,4- endo-methylene group of 10 2- of embodiment-naphthalene -9- phenol (IV)
The mass ratio of the material that feeds intake is [2,3]-epoxy -5- nitro -1,2,3,4- tetrahydro -1,4- endo-methylene group-naphthalene (III):
48% hydrobromic acid aqueous solution=1:10
In the 500ml there-necked flask equipped with mechanical stirring and thermometer, 48% hydrobromic acid aqueous solution of addition (177.2g,
1.05mol), at 20 DEG C, [2,3]-epoxy -5- nitro -1,2,3,4- tetrahydros-Isosorbide-5-Nitrae-endo-methylene group-naphthalene (III) is added dropwise
After the dichloromethane solution 130ml, 1.5h of (14.3g, 0.07mol), charging terminates, insulated and stirred 5min, is tracked and is reacted with TLC
Situation.After reaction, liquid separation is stood, organic layer washed 2 times with 25ml saturated sodium bicarbonate solution, then with 40ml saturated salt solution
Wash primary, liquid separation, the dry concentration of organic layer obtains khaki solid, and the mixed solvent of crude product n-hexane and ethyl acetate is tied again
It is brilliant that the bromo- 5- nitro -1,2 of white solid 2-, 3,4- tetrahydros-Isosorbide-5-Nitrae-endo-methylene group-naphthalene -9- phenol (IV) obtain 13.1g after dry
Compound (IV), 132.1 DEG C -133.2 DEG C of fusing point, yield 66.1%.
The synthesis of the bromo- 5- nitro -1,2,3,4- tetrahydro -1,4- endo-methylene group of 11 2- of embodiment-naphthalene -9- phenol (IV)
The mass ratio of the material that feeds intake is [2,3]-epoxy -5- nitro -1,2,3,4- tetrahydro -1,4- endo-methylene group-naphthalene (III):
48% hydrobromic acid aqueous solution=1:5
48% hydrobromic acid aqueous solution inventory is 59.1g, remaining inventory and operating process are the same as embodiment 1.Obtain the bromo- 5- of 2-
Nitro -1,2,3,4- tetrahydros-Isosorbide-5-Nitrae-endo-methylene group-naphthalene -9- phenol (IV) 9.7g, yield 49.2%, 132.1 DEG C -133.3 of fusing point
℃。
The synthesis of the bromo- 5- nitro -1,2,3,4- tetrahydro -1,4- endo-methylene group of 12 2- of embodiment-naphthalene -9- phenol (IV)
The mass ratio of the material that feeds intake is [2,3]-epoxy -5- nitro -1,2,3,4- tetrahydro -1,4- endo-methylene group-naphthalene (III):
48% hydrobromic acid aqueous solution=1:20
48% hydrobromic acid aqueous solution inventory is 236.2g, remaining inventory and operating process are the same as embodiment 1.It is bromo- to obtain 2-
5- nitro -1,2,3,4- tetrahydros-Isosorbide-5-Nitrae-endo-methylene group-naphthalene -9- phenol (IV) 11.8g, yield 59.6%, 132.1 DEG C of fusing point -
133.4℃。
The synthesis of the bromo- 5- nitro -1,2,3,4- tetrahydro -1,4- endo-methylene group of 13 2- of embodiment-naphthalene -9- phenol (IV)
The mass ratio of the material that feeds intake is [2,3]-epoxy -5- nitro -1,2,3,4- tetrahydro -1,4- endo-methylene group-naphthalene (III):
48% hydrobromic acid aqueous solution=1:1.
48% hydrobromic acid aqueous solution inventory is 11.8g, remaining inventory and operating process are the same as embodiment 1.Obtain the bromo- 5- of 2-
Nitro -1,2,3,4- tetrahydros-Isosorbide-5-Nitrae-endo-methylene group-naphthalene -9- phenol (IV) 4.1g, yield 20.7%, 131.9 DEG C -133.5 of fusing point
℃。
The synthesis of 14 5- amino -1,2,3,4- tetrahydro -1,4- endo-methylene group of embodiment-naphthalene -9- phenol (V)
The mass ratio that feeds intake is the bromo- 5- nitro -1,2,3,4- tetrahydro -1,4- endo-methylene group of 2--naphthalene -9- phenol: 5%Pd/C=1:
0.03, triethylamine dosage is 3 equivalents.
The bromo- 5- nitro -1,2,3,4- tetrahydro -1,4- endo-methylene group of 2--naphthalene -9- phenol is added into 500ml autoclave
(2.83g, 0.01mol), catalyst 5%Pd/C 0.08g, triethylamine (3.0g, 0.03mol), dehydrated alcohol (300ml), in kettle
Hydrogen Vapor Pressure 3.0MPa at 120 DEG C of temperature, stirs 5h, and after raw material conversion completely, catalyst 5%Pd/C, filter are recycled in filtering
After liquid concentration, water and each 20ml of ethyl acetate is added, after stirring 10min at room temperature, stratification, organic layer is dry, is concentrated, and obtains
5- amino -1,2,3,4- tetrahydros-Isosorbide-5-Nitrae-endo-methylene group-naphthalene -9- phenol (V) 1.68g, yield 96.0%, G/C content 97.1%.[GC
Method: Fu Li 9790II type gas chromatograph；Chromatographic column: SE-54；Sample injector: 330 DEG C；Detector: 340 DEG C；Column temperature: at 200 DEG C
2min is kept the temperature, 1 DEG C/min rises to 220 DEG C, 220 DEG C of 3min, 5 DEG C/min is kept to rise to 250 DEG C, then keeps 250 DEG C of constant temperature].
The synthesis of 15 5- amino -1,2,3,4- tetrahydro -1,4- endo-methylene group of embodiment-naphthalene -9- phenol (V)
The mass ratio that feeds intake is the bromo- 5- nitro -1,2,3,4- tetrahydro -1,4- endo-methylene group of 2--naphthalene -9- phenol: 5%Pd/C=1:
0.1, triethylamine dosage is 5 equivalents.
The bromo- 5- nitro -1,2,3,4- tetrahydro -1,4- endo-methylene group of 2--naphthalene -9- phenol is added into 500ml autoclave
(50.9g, 0.18mol), 5%Pd/C 0.51g, triethylamine (90.9g, 0.90mol), dehydrated alcohol (300ml), hydrogen in kettle
Pressure 3.5MPa at 120 DEG C of temperature, stirs 6h, and after raw material conversion completely, catalyst 5%Pd/C is recycled in filtering, and filtrate is dense
After contracting, water and each 200ml of ethyl acetate is added, after stirring 10min at room temperature, stratification, organic layer is dry, is concentrated, and obtains 5-
Amino -1,2,3,4- tetrahydros-Isosorbide-5-Nitrae-endo-methylene group-naphthalene -9- phenol (V) 25.2g, yield 80.0%, G/C content 93.2%.Gas phase inspection
Survey condition is the same as embodiment 14.
The synthesis of 16 5- amino -1,2,3,4- tetrahydro -1,4- endo-methylene group of embodiment-naphthalene -9- phenol (V)
The mass ratio that feeds intake is the bromo- 5- nitro -1,2,3,4- tetrahydro -1,4- endo-methylene group of 2--naphthalene -9- phenol: 5%Pd/C=1:
0.05, triethylamine dosage is 3 equivalents.
The bromo- 5- nitro -1,2,3,4- tetrahydro -1,4- endo-methylene group of 2--naphthalene -9- phenol is added into 500ml autoclave
(8.5g, 0.03mol), 5%Pd/C 0.43g, triethylamine (15.2g, 0.15mol), anhydrous methanol (300ml), hydrogen pressure in kettle
Power 2.0MPa at 120 DEG C of temperature, stirs 5h, and after raw material conversion completely, catalyst 5%Pd/C, filtrate concentration are recycled in filtering
Afterwards, water and each 50ml of ethyl acetate is added, after stirring 10min at room temperature, stratification, organic layer is dry, is concentrated, and obtains 5- ammonia
Base -1,2,3,4- tetrahydros-Isosorbide-5-Nitrae-endo-methylene group-naphthalene -9- phenol (V) 4.9g, yield 93.3%, G/C content 92.8%.Vapor detection
Condition is the same as embodiment 14.
17 N- of embodiment (1,2,3,4- tetrahydro -1,4- endo-methylene group-naphthalene -9- carbonyl -5- base -)-phthalimide
(VII) synthesis.
The mass ratio of the material that feeds intake is N- (1,2,3,4- tetrahydro -1,4- endo-methylene group-naphthalene -9- phenol -5- base -)-O-phthalic
Acid imide: TEMPO:TCCA: sodium bromide=1:0.02:1.3:0.2
Mechanical stirring is being housed, in the 500ml there-necked flask of thermometer and constant pressure funnel, N- (1,2,3,4- tetra- is added
Hydrogen-Isosorbide-5-Nitrae-endo-methylene group-naphthalene -9- phenol -5- base -)-phthalimide (10.0g, 32.8mmol) and ethyl acetate
(200ml) opens stirring, TEMPO (0.1g, 0.65mmol) is added at 0 DEG C, sodium bromide (0.66g, 6.5mmol), charging knot
Then the ethyl acetate solution (100ml) of TCCA (9.8g, 42.6mmol) is added dropwise in insulated and stirred 10min after beam, feed knot after 1h
Beam stirs 1h at 0 DEG C, after reaction, saturated sodium bisulfite solution 10ml is added into reaction flask, stirs 1h at room temperature,
Water 200ml is added, after stirring 10min, stands liquid separation, organic layer concentration obtains N- (1,2,3,4- tetrahydro-Isosorbide-5-Nitrae-endo-methylene group-
Naphthalene -9- carbonyl -5- base -)-phthalimide (VII) 9.4g, yield 94.6%.
18 N- of embodiment (1,2,3,4- tetrahydro -1,4- endo-methylene group-naphthalene -9- dichloro methene -5- base -)-O-phthalic
The synthesis of acid imide (VIII)
The mass ratio of the material that feeds intake is N- (1,2,3,4- tetrahydro -1,4- endo-methylene group-naphthalene -9- carbonyl -5- base -)-adjacent benzene two
Carboximide: triphenylphosphine: carbon tetrachloride=1:3:2
Mechanical stirring is being housed, in the 500ml there-necked flask of thermometer and constant pressure funnel, N- (1,2,3,4- tetra- is added
Hydrogen-Isosorbide-5-Nitrae-endo-methylene group-naphthalene -9- carbonyl -5- base -)-phthalimide (12.1g, 0.04mol), triphenylphosphine
(31.4g, 0.12mol) and acetonitrile (100ml) opens stirring, carbon tetrachloride is added dropwise at 60 DEG C after nitrogen displacement three times
(12.3g, 0.08mol), after completion of dropwise addition, insulated and stirred 1h, after reaction, reaction solution concentration, then be added into concentrate
40ml methanol, after standing refrigeration 3h, filtering obtains N- (1,2,3,4- tetrahydro-Isosorbide-5-Nitrae-endo-methylene group-naphthalene -9- dichloro methene -5-
Base -)-phthalimide (VIII) 12.6g, yield 85.4%.
The synthesis of 19 9- of embodiment (dichloro methene) -1,2,3,4- tetrahydro -5- amino naphthalenes (IX)
The mass ratio of the material that feeds intake is N- (1,2,3,4- tetrahydro -1,4- endo-methylene group-naphthalene -9- dichloro methene -5- base -) -
Phthalimide: 40% methylamine water solution=1:6
Mechanical stirring is being housed, in the 500ml there-necked flask of thermometer and constant pressure funnel, N- (1,2,3,4- tetra- is added
Hydrogen-Isosorbide-5-Nitrae-endo-methylene group-naphthalene -9- dichloro methene -5- base -)-phthalimide (11.1g, 0.03mol) and ethyl alcohol
(100ml) is added dropwise 40% methylamine water solution (13.9g, 0.18mol) at 90 DEG C, and feeding after 0.5h terminates, then insulated and stirred
Ethyl acetate (30ml) and water (50ml), liquid separation are added into concentrate by 3h, after reaction, reaction solution concentration, and organic layer is done
Dry, concentration, obtains 9- (dichloro methene) -1,2,3,4- tetrahydro -5- amino naphthalenes (IX) 6.1g, yield 85.1%.HPLC content:
99.4%.[HPLC method: chromatographic column: 4.6mm × 150mm × 5 μm XDB-C18；Mobile phase: methanol: water=65:35；Detect wave
Long 216nm；Column temperature: 30 DEG C；Flow velocity 1.0ml/min]..
The synthesis of 20 9- of embodiment (dichloro methene) -1,2,3,4- tetrahydro -5- amino naphthalenes (IX)
The mass ratio of the material that feeds intake is N- (1,2,3,4- tetrahydro -1,4- endo-methylene group-naphthalene -9- dichloro methene -5- base -) -
Phthalimide: 80% hydrazine hydrate solution=1:4
The dosage of 80% hydrazine hydrate solution is 7.4g (0.12mol), remaining inventory and operating process are obtained with embodiment 19
9- (dichloro methene) -1,2,3,4- tetrahydro -5- amino naphthalenes (IX) 6.3g, yield 87.9%, HPLC content 99.5%.Liquid phase inspection
Survey method is the same as embodiment 19.
21 3- difluoromethyl -1- methyl-1 H- pyrazoles -4- carboxylic acid (9- dichloromethylene -1,2,3,4- tetrahydro-of embodiment
1,4- endo-methylene group-naphthalene -5- base)-amide (IX) synthesis
The mass ratio of the material that feeds intake is 9- (dichloro methene) -1,2,3,4- tetrahydro -5- amino naphthalenes: 3- difluoromethyl -1- first
Base -1H- pyrazoles -4- phosgene: triethylamine=1:1.01:2
In the 500ml there-necked flask equipped with mechanical stirring, constant pressure funnel and tail gas absorber, 9- (dichloromethane is added
Alkenyl) -1,2,3,4- tetrahydro -5- amino naphthalenes (23.9g, 0.1mol), methylene chloride 100ml and triethylamine (20.2g,
0.2mol), stirring is opened, 3- difluoromethyl -1- methyl-1 H- pyrazoles -4- phosgene is added dropwise at 0 DEG C, after charging, is protected
Temperature reaction completely, water 20ml is added into reaction flask, is stirred at room temperature 10 minutes, stands liquid separation, organic layer to raw material conversion
Dry, concentration, obtains 3- difluoromethyl -1- methyl-1 H- pyrazoles -4- carboxylic acid (9- dichloromethylene -1,2,3,4- tetrahydros-Isosorbide-5-Nitrae-bridge
Methylene-naphthalene -5- base)-amide (IX) 39.3g, yield 98.9%.HPLC purity (area normalization method) 98.7%, fusing point
148.7-149.2 DEG C, physicochemical data and document Tobler, H.；Walter,H.；Ehrenfreund,J.；Corsi,
C.WO2007/048556,2007(Syngenta)；Chem.Abstr.
2007,146,481833 reports are consistent.[HPLC method: chromatographic column: 4.6mm × 150mm × 5 μm XDB-C18；Flowing
Phase: acetonitrile: phosphonic acids aqueous solution (1:1000)=70:30；Detection wavelength 255nm；Column temperature: 40 DEG C；Flow velocity 1.0ml/min].
Claims (9)
1. structural formula N- as shown in (VI) (1,2,3,4- tetrahydro -1,4- endo-methylene group-naphthalene -9- phenol -5- base)-phthalyl is sub-
Amine
2. preparing compound N-described in claim 1 (1,2,3,4- tetrahydro -1,4- endo-methylene group-naphthalene -9- phenol -5- base)-neighbour
The method of phthalimide, it is characterised in that: with formula (V) compound represented 5- amino -1,2,3,4- tetrahydros-Isosorbide-5-Nitrae-bridge is sub-
Under 120 DEG C of -150 DEG C of molten conditions after reaction, organic solvent is added in methyl-naphthalene -9- phenol and phthalic anhydride, is made
Formula (VI) compound
3. according to the method described in claim 2, it is characterized by: the organic solvent is toluene, dimethylbenzene, chlorobenzene or ring
Pentanone.
4. according to the method described in claim 2, it is characterized by: the mass ratio of the material that feeds intake in the method is compound
(V): phthalic anhydride 1: 1.01-1.2；The consumption of organic solvent is 2 times of compound (V) quality.
5. preparing compound N-as claimed in claim 2 (1,2,3,4- tetrahydro -1,4- endo-methylene group-naphthalene -9- phenol -5- base)-neighbour
The method of phthalimide, it is characterised in that: processing step is as follows:
1) 5- nitro -1,4- dihydro -1,4- endo-methylene group-naphthalene preparation
By methylene chloride, catalyst I is added in reaction kettle, and co-catalyst II and 2- amino-is added dropwise simultaneously under 40 DEG C of stirrings
The acetone soln of 6- nitrobenzoic acid and cyclopentadiene after charging, is warming up to 50 DEG C and is stirred to react 3h, to the end of reacting,
Reaction solution is filtered with diatomite, filtrate concentration, and with n-hexane refluxing extraction, obtains 5- nitro-Isosorbide-5-Nitrae-dihydro-Isosorbide-5-Nitrae-bridge methylene
Base-naphthalene, the catalyst I are the concentrated sulfuric acid, and the co-catalyst II is isoamyl nitrite or nitrite tert-butyl；
2) [2,3]-epoxy -5- nitro -1,2,3,4- tetrahydro -1,4- endo-methylene group-naphthalene preparation
5- nitro -1,4- dihydro -1,4- endo-methylene group-the naphthalene and 1,2- dichloroethanes wiring solution-forming that step 1) is obtained；To anti-
It answers and metachloroperbenzoic acid is added in kettle, with 1,2- dichloroethanes for solvent, stir lower dropwise addition 5- nitro-Isosorbide-5-Nitrae-dihydro-Isosorbide-5-Nitrae-
Endo-methylene group-naphthalene solution, charging terminate, and are warming up to 60 DEG C and are stirred to react 1.5h, after reaction, it is molten that saturated sodium sulfite are added
Liquid, liquid separation, organic layer alkali cleaning, concentration obtain [2,3]-epoxy -5- nitro -1,2,3,4- tetrahydros-Isosorbide-5-Nitrae-endo-methylene group-naphthalene；
3) the bromo- 5- nitro -1,2,3,4- tetrahydro -1,4- endo-methylene group of 2--naphthalene -9- phenol preparation
[2,3]-epoxy -5- nitro -1,2,3,4- tetrahydro -1,4- endo-methylene group-naphthalene and organic solvent that step 2) obtains are matched
At solution；Hydrobromic acid aqueous solution is added into reaction kettle, at 20 DEG C, dropwise addition [2,3]-epoxy -5- nitro -1,2,3,4- tetra-
Hydrogen-Isosorbide-5-Nitrae-endo-methylene group-naphthalene solution, charging terminate, and are stirred to react 5min, after reaction, liquid separation, organic layer is washed till neutrality
Afterwards, dry, concentration obtains the bromo- 5- nitro -1,2 of 2-, 3,4- tetrahydros-Isosorbide-5-Nitrae-endo-methylene group-naphthalene -9- phenol；
4) 5- amino -1,2,3,4- tetrahydro -1,4- endo-methylene group-naphthalene -9- phenol preparation
The bromo- 5- nitro -1,2 of the 2- that step 3) is obtained, 3,4- tetrahydros-Isosorbide-5-Nitrae-endo-methylene group-naphthalene -9- phenol are added in reaction kettle,
Using dehydrated alcohol or anhydrous methanol as solvent, metallic catalyst IV and co-catalyst V is added, heating stirring is anti-under Hydrogen Vapor Pressure
It answers 5-6 hours, to fully reacting, reaction solution is filtered, filtrate is distilled to recover solvent, obtains 5- amino -1,2,3,4- tetrahydros-Isosorbide-5-Nitrae -
Endo-methylene group-naphthalene -9- phenol, the metallic catalyst IV is any one in Pd/C, Rh/C, Pt/C or Raney's nickel, described to help
Catalyst V is any one in triethylamine, diisopropylethylamine or pyridine；
5) preparation of N- (1,2,3,4- tetrahydro -1,4- endo-methylene group-naphthalene -9- phenol -5- base)-phthalimide
5- amino -1,2 that step 4) is obtained, 3,4- tetrahydros-Isosorbide-5-Nitrae-endo-methylene group-naphthalene -9- phenol are added in reaction kettle, are added adjacent
Phthalate anhydride, heating melting under solvent-free conditions is stirred to react 1.5h, and to the end of reacting, organic solvent VI is added dropwise while hot,
After being cooled to room temperature, filtering obtains the adjacent benzene of shallow white solid N- (1,2,3,4- tetrahydro-Isosorbide-5-Nitrae-endo-methylene group-naphthalene -9- phenol -5- base) -
Dicarboximide, the organic solvent VI are any one in dimethylbenzene, cyclopentanone, chlorobenzene or toluene.
6. N- (1,2,3,4- tetrahydro -1,4- endo-methylene group-naphthalene -9- phenol -5- base)-phthalyl described in claim 1 is sub-
Amine preparation such as formula (X) compound represented 3- difluoromethyl -1- methyl-1 H- pyrazoles -4- carboxylic acid-(dichloromethylene -1 9-,
2,3,4- tetrahydro -1,4- endo-methylene group-naphthalene -5- base) application in-amide.
7. N- (1,2,3,4- tetrahydro -1,4- endo-methylene group-naphthalene -9- phenol -5- base)-phthalyl described in claim 1 is sub-
Amine preparation such as formula (X) compound represented 3- difluoromethyl -1- methyl-1 H- pyrazoles -4- carboxylic acid-(dichloromethylene -1 9-,
2,3,4- tetrahydros-Isosorbide-5-Nitrae-endo-methylene group-naphthalene -5- base)-amide method, it is characterised in that:
Processing step is as follows:
1) preparation of N- (1,2,3,4- tetrahydro -1,4- endo-methylene group-naphthalene -9- carbonyl -5- base)-phthalimide
N- (1,2,3,4- tetrahydro-Isosorbide-5-Nitrae-endo-methylene group-naphthalene -9- phenol -5- base)-phthalimide is added in reaction kettle,
Using ethyl acetate as solvent, stirring is opened, oxidant VII, sodium bromide and trichloroisocyanuric acid are added at 0 DEG C, wait react knot
Saturated sodium thiosulfate solution is added into reaction kettle by Shu Hou, and after stirring 0.5h, reaction solution washes liquid separation, and organic layer concentration obtains
N- (1,2,3,4- tetrahydro-Isosorbide-5-Nitrae-endo-methylene group-naphthalene -9- carbonyl -5- base)-phthalimide, the oxidant VII are
It is any one in 2,2,6,6- tetramethyl piperidine-nitrogen-oxide or 4- hydroxyl -2,2,6,6- tetramethyl piperidine -1- oxygen radical
Kind；
2) preparation of N- (1,2,3,4- tetrahydro -1,4- endo-methylene group-naphthalene -9- dichloro methene -5- base)-phthalimide
N- (1,2,3,4- tetrahydro -1,4- endo-methylene group-naphthalene -9- carbonyl -5- base)-phthalimide that step 1) is obtained
It is added in reaction kettle, using acetonitrile as solvent, triphenylphosphine is added, after nitrogen displacement, heating is added with stirring carbon tetrachloride, to anti-
After answering, reaction solution concentration, after methanol is added thereto and stands refrigeration 3h, filtering obtains N- (1,2,3,4- tetrahydro-Isosorbide-5-Nitrae-
Endo-methylene group-naphthalene -9- dichloro methene -5- base)-phthalimide；
3) preparation of 9- (dichloro methene) -1,2,3,4- tetrahydro -5- amino naphthalenes
N- (1,2,3,4- tetrahydro -1,4- endo-methylene group-naphthalene -9- dichloro methene -5- base)-O-phthalic that step 2) is obtained
Acid imide is added in reaction kettle, and using ethyl alcohol as solvent, heating is added with stirring alkaline reagent, to which after reaction, reaction solution is dense
Ethyl acetate is added into concentrate for contracting recycling design, washes liquid separation, and organic layer concentration obtains white solid 9- (dichloro methylene
Base) -1,2,3,4- tetrahydro -5- amino naphthalenes, the alkaline reagent is any one in hydrazine hydrate solution or methylamine water solution；
4) 3- difluoromethyl -1- methyl-1 H- pyrazoles -4- carboxylic acid-(9- dichloromethylene -1,2,3,4- tetrahydro -1,4- bridge methylene
Base-naphthalene -5- base)-amide preparation
- 1,2,3, the 4- tetrahydro -5- amino naphthalenes of 9- (dichloro methene) that step 3) is obtained are added in reaction kettle, and solvent is added
VIII and triethylamine open stirring, 3- difluoromethyl -1- methyl-1 H- pyrazoles -4- phosgene are added dropwise at 0 DEG C, to the end of reacting
Afterwards, wash, liquid separation, organic layer concentration, obtain 3- difluoromethyl -1- methyl-1 H- pyrazoles -4- carboxylic acid-(9- dichloromethylene -1,2,
3,4- tetrahydros-Isosorbide-5-Nitrae-endo-methylene group-naphthalene -5- base)-amide, the solvent VIII is ethyl acetate, butyl acetate, dichloromethane
Any one in alkane, 1,2- dichloroethanes, toluene, dimethylbenzene or chlorobenzene.
8. according to the method described in claim 7, it is characterized by: oxidant VII described in step 1) is 2,2,6,6- tetramethyls
Phenylpiperidines-nitrogen-oxide, N- (1,2,3,4- tetrahydro-Isosorbide-5-Nitrae-endo-methylene group-naphthalene -9- phenol -5- base)-phthalimide and
2,2,6,6- tetramethyl piperidine-nitrogen-oxide molar ratio is 1:0.01-0.1.
9. according to the method described in claim 7, it is characterized in that the concentration of hydrazine hydrate solution described in step 3) is 80%, N-
(1,2,3,4- tetrahydro -1,4- endo-methylene group-naphthalene -9- dichloro methene -5- base)-phthalimide and 80% hydrazine hydrate are molten
The molar ratio of liquid or 40% methylamine water solution is 1:1-8, and reaction temperature is 85-90 DEG C.
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| CN102026982A (en) * | 2008-05-14 | 2011-04-20 | 先正达参股股份有限公司 | Process for the preparation of amides |
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